GATA‐binding protein 3, gross cystic disease fluid protein‐15 and mammaglobin have distinct prognostic implications in different invasive breast carcinoma subgroups
Abstract:The commonly used breast carcinoma biomarkers vary in their prognostic implications. GCDFP-15 independently indicated a favourable prognosis, especially in ER-negative, HER2-positive and molecular apocrine cancers. GATA-3 and MGB were not associated with outcome.
“…Expression of GATA3, GCDFP15 and MGB has been reported in 32-100%, 23-78% and 48-73% of IBCs, respectively. [1][2][3][4][5][6][7][8][9][10][11][12] These markers showed high expression in hormonal receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)positive cancers, but low expression in triple-negative breast cancers (TNBCs). 1,4,6,12,13 Some studies reported GATA3 expression in >90% of HR-positive cancers, whereas only 20-66% of TNBCs showed expression when a certain clone of GATA3 (L50-823) was used.…”
Sry-related high-mobility-group/HMG box 10 (SOX10) as a sensitive marker for triple-negative breast cancer Aims: Confirmation of a breast origin for triple-negative breast cancer (TNBC) is sometimes problematic. The traditional breast markers GATA-binding protein 3 (GATA3), mammaglobin (MGB) and gross cystic disease fluid protein 15 (GCDFP15) have shown limitations in identifying TNBC. Here, we aimed to examine the diagnostic potential of the newly proposed TNBC marker, Sry-related high-mobility-group/HMG box 10 (SOX10). Methods and results: We analysed and compared SOX10 expression with GATA3, MGB and GCDFP15 expression in a test cohort of 1838 invasive breast cancers (IBCs) by using tissue microarrays. The findings from the test cohort were further examined with a validation cohort of 42 TNBCs in whole sections. The overall expression rates of SOX10, GATA3, MGB and GCDFP15 were 6.9%, 83.1%, 47.0%, and 34.8%, respectively. Among the TNBCs within this cohort, the expression rates of SOX10, GATA3, MGB and GCDFP15 were 31.3%, 34.5%, 27.9%, and 25.2%, respectively. SOX10 was strongly associated with TNBC (P < 0.001), whereas all other traditional markers were associated with non-TNBC (P < 0.001 for all). In addition, SOX10 was more correlated to basal-like breast cancer (BLBC) (P = 0.001) than five-marker-negative subtype among the TNBCs. A high expression rate of SOX10 (81%) was confirmed in the validation cohort. Additionally, SOX10 expression was inversely correlated with GATA3 and GCDFP15 expression, so they may complement each other in TNBC detection. The SOX10-GATA3 combination yielded a sensitivity of 60.3% for TNBC detection in the test cohort. Conclusion: SOX10 is a reliable marker for identifying TNBC, and complements GATA3. The SOX10-GATA3 combination may be used as a sensitive TNBC marker.
“…Expression of GATA3, GCDFP15 and MGB has been reported in 32-100%, 23-78% and 48-73% of IBCs, respectively. [1][2][3][4][5][6][7][8][9][10][11][12] These markers showed high expression in hormonal receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)positive cancers, but low expression in triple-negative breast cancers (TNBCs). 1,4,6,12,13 Some studies reported GATA3 expression in >90% of HR-positive cancers, whereas only 20-66% of TNBCs showed expression when a certain clone of GATA3 (L50-823) was used.…”
Sry-related high-mobility-group/HMG box 10 (SOX10) as a sensitive marker for triple-negative breast cancer Aims: Confirmation of a breast origin for triple-negative breast cancer (TNBC) is sometimes problematic. The traditional breast markers GATA-binding protein 3 (GATA3), mammaglobin (MGB) and gross cystic disease fluid protein 15 (GCDFP15) have shown limitations in identifying TNBC. Here, we aimed to examine the diagnostic potential of the newly proposed TNBC marker, Sry-related high-mobility-group/HMG box 10 (SOX10). Methods and results: We analysed and compared SOX10 expression with GATA3, MGB and GCDFP15 expression in a test cohort of 1838 invasive breast cancers (IBCs) by using tissue microarrays. The findings from the test cohort were further examined with a validation cohort of 42 TNBCs in whole sections. The overall expression rates of SOX10, GATA3, MGB and GCDFP15 were 6.9%, 83.1%, 47.0%, and 34.8%, respectively. Among the TNBCs within this cohort, the expression rates of SOX10, GATA3, MGB and GCDFP15 were 31.3%, 34.5%, 27.9%, and 25.2%, respectively. SOX10 was strongly associated with TNBC (P < 0.001), whereas all other traditional markers were associated with non-TNBC (P < 0.001 for all). In addition, SOX10 was more correlated to basal-like breast cancer (BLBC) (P = 0.001) than five-marker-negative subtype among the TNBCs. A high expression rate of SOX10 (81%) was confirmed in the validation cohort. Additionally, SOX10 expression was inversely correlated with GATA3 and GCDFP15 expression, so they may complement each other in TNBC detection. The SOX10-GATA3 combination yielded a sensitivity of 60.3% for TNBC detection in the test cohort. Conclusion: SOX10 is a reliable marker for identifying TNBC, and complements GATA3. The SOX10-GATA3 combination may be used as a sensitive TNBC marker.
“…GATA3 has been studied extensively in a number of tumour types, including breast and urothelial carcinomas for use as an adjunct to diagnosis . However, although GATA3 has long been associated with ER expression in luminal breast carcinomas and is used frequently to support the origin of metastatic tumours, there has been an increasing number of publications documenting both protein and gene expression in triple‐negative breast cancers (TNBC) . Indeed, Hou et al .…”
Section: Introductionmentioning
confidence: 99%
“…[14][15][16] However, although GATA3 has long been associated with ER expression in luminal breast carcinomas and is used frequently to support the origin of metastatic tumours, 15,[17][18][19][20][21] there has been an increasing number of publications documenting both protein and gene expression in triple-negative breast cancers (TNBC). 15,[20][21][22][23][24] Indeed, Hou et al 25 recently reported more than 23% of primary and 26% of metastatic TNBCs to be GATA3-positive using immunohistochemisty.…”
Our study has demonstrated that GATA3 expression is common in primary triple-negative breast carcinomas. It also suggests that although GATA3 is an oestrogen receptor (ER) regulated gene, it still proves useful in differentiating between primary and metastatic tumours in patients with a history of breast cancer regardless of its molecular subtype.
“…Loss of GATA3 expression has been associated with unfavorable clinical outcome and worse survival [15,[23][24]. However, no association with outcome has been observed in other studies [25]. In one study, GATA3 expression was found to be associated with favorable outcome in all the breast tumors in the study, while the association was lost when only ER positive cancers were analyzed [26].…”
Background: Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited.
Methods: This study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival.
Results: CK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P=0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2 % of Grade 1 cases were GATA3 negative (P<0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor.
Conclusions: More CK7 negative and GATA3 negative tumors were seen in breast cancer of high histologic grade. GATA3 expression was associated with ER status. Lack of CK7 and GATA3 expression in Grade 3 breast cancer was not associated with patient outcome.
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